Jaw Problem Tied to Bisphosphonates

BOSTON—IV bisphosphonates may increase the risk of osteonecrosis of the jaw (ONJ), according to new findings.

Researchers at the New York Harbor Health Care System, Brooklyn campus, reviewed the charts of 1,951 patients receiving bisphosphonates and undergoing dental treatment. The investigators identified two patients with ONJ. Both had been diagnosed with multiple myeloma and had received chemotherapy and steroids in addition to IV bisphosphonate therapy. They initially received pamidronate (Aredia) for several years before being switched to zolendronate (Zometa). In each case, ONJ occurred after routine dental extraction leading to exposed bone at the extraction site. One patient had been on bisphosphonate therapy for six years and the second patient had been on bisphosphonate therapy for eight years.

“We are probably the fourth or fifth study looking at this and the findings have all been similar,” said lead investigator Omar Murad, MD, an endocrinology fellow at the State University of New York, HealthSciencesCenter in Brooklyn. “I think the mechanism of action is avascularization of the jaw by bisphosphonates, but it seems that bisphos-phonate therapy is not enough. There appears to be a need for a background of chemotherapy and steroids, which may be affecting the immune system.”

He said these findings should be of particular concern to urologists who are managing prostate cancer patients on IV bisphosphonates. He recommends that physicians counsel their prostate cancer patients to have a dental checkup before starting on parenteral bisphosphonates.

Dr. Murad, who presented the study findings at annual meeting of The Endocrine Society, said the prevalence of ONJ was estimated to be 1 in 72 for the patients in this study who received IV bisphosphonates. The overall prevalence of ONJ is approximately 1 in 1,000 in all the cases reviewed (with and without bisphosphonate use). In the general population, the prevalence currently is estimated to be 1 in 2,200-5,000 among adults.

Although the number of ONJ cases may be low right now, this is a serious issue because so many adults are taking bisphosphonates, Dr. Murad said. Patients without cancer who are taking oral bisphosphonates may be at very low risk, but that may not be the case for patients receiving cancer therapies and parenteral bisphosphonates.

“These patients already have a deterioration of their quality of life because of their cancer and their chemotherapy and steroids. Now they have a hole in their jaw and they cannot eat. They cannot drink and it is extremely painful and all the clinicians are doing today is just helping to control the pain.”

Little is known about ONJ, for which no universally accepted definition exists. The condition typically appears as an area of exposed bone in the lower or upper jaw. Often, this exposed bone develops after a recent tooth extraction, mouth injury, or dental surgery for infection. However, cases of ONJ have occurred when there is no known preceding injury.

Insufficient data exist at this time to construct evidence-based guidelines for prevention and treatment of ONJ. Patients on bisphosphonate therapy for cancer, osteoporosis, or Paget's

disease should seek medical advice before any invasive dental procedures, according to the American Society for Bone and Mineral Research. The society announced in July that it is forming a new task force to help examine the relationship between bisphosphonates and ONJ. Patients beginning or taking bisphosphonate therapy should be informed of possible risks, including ONJ.